Institute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.
Stem Cells. 2022 Jul 27;40(7):630-640. doi: 10.1093/stmcls/sxac027.
The subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) is a neurogenic niche of the adult brain that contains neural stem cells (NSCs) able to generate excitatory glutamatergic granule neurons, which integrate into the DG circuit and contribute to hippocampal plasticity, learning, and memory. Thus, endogenous NSCs could be harnessed for therapeutic purposes. In this context, it is critical to characterize the molecular mechanisms controlling the generation and functional integration of adult-born neurons. Adult hippocampal neurogenesis is tightly controlled by both cell-autonomous mechanisms and the interaction with the complex niche microenvironment, which harbors the NSCs and provides the signals to support their maintenance, activation, and differentiation. Among niche-derived factors, Wnt ligands play diverse roles. Wnts are secreted glycoproteins that bind to Frizzled receptors and co-receptors to trigger the Wnt signaling pathway. Here, we summarize the current knowledge about the roles of Wnts in the regulation of adult hippocampal neurogenesis. We discuss the possible contribution of the different niche cells to the regulation of local Wnt signaling activity, and how Wnts derived from different cell types could induce differential effects. Finally, we discuss how the effects of Wnt signaling on hippocampal network activity might contribute to neurogenesis regulation. Although the evidence supports relevant roles for Wnt signaling in adult hippocampal neurogenesis, defining the cellular source and the mechanisms controlling secretion and diffusion of Wnts will be crucial to further understand Wnt signaling regulation of adult NSCs, and eventually, to propose this pathway as a therapeutic target to promote neurogenesis.
海马齿状回的颗粒下区（SGZ）是成人脑的一个神经发生龛位，其中包含能够产生兴奋性谷氨酸能颗粒神经元的神经干细胞（NSC），这些神经元整合到 DG 回路中，并有助于海马体的可塑性、学习和记忆。因此，内源性 NSCs 可以被用于治疗目的。在这种情况下，对控制成年产生神经元的生成和功能整合的分子机制进行特征描述至关重要。成年海马体神经发生受到细胞自主机制和与复杂龛位微环境相互作用的严格控制，该微环境包含 NSCs 并提供支持其维持、激活和分化的信号。在龛位衍生因子中，Wnt 配体发挥着多样化的作用。Wnts 是分泌的糖蛋白，可与 Frizzled 受体和共受体结合，从而触发 Wnt 信号通路。在这里，我们总结了 Wnts 在调节成年海马体神经发生中的作用的最新知识。我们讨论了不同龛位细胞对局部 Wnt 信号活性调节的可能贡献，以及来自不同细胞类型的 Wnts 如何诱导不同的效应。最后，我们讨论了 Wnt 信号对海马体网络活动的影响如何有助于神经发生的调节。尽管有证据表明 Wnt 信号在成年海马体神经发生中具有重要作用，但确定 Wnt 信号的细胞来源以及控制其分泌和扩散的机制对于进一步理解 Wnt 信号对成年 NSCs 的调节以及最终将该途径作为促进神经发生的治疗靶点至关重要。
